chr4-182753544-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001080477.4(TENM3):c.3957C>T(p.Gly1319Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,612,446 control chromosomes in the GnomAD database, including 36,452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2765 hom., cov: 33)

Exomes 𝑓: 0.21 ( 33687 hom. )

Consequence

TENM3
NM_001080477.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.505

Publications

17 publications found

Variant links:

Genes affected

TENM3 (HGNC:29944): (teneurin transmembrane protein 3) This gene encodes a member of the teneurin transmembrane protein family. The encoded protein may be involved in the regulation of neuronal development including development of the visual pathway. Mutations in this gene have been associated with microphthalmia and developmental dysplasia of the hip. [provided by RefSeq, Jan 2023]

TENM3 Gene-Disease associations (from GenCC):

microphthalmia, isolated, with coloboma 9
Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
microphthalmia, isolated, with coloboma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TENM3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 4-182753544-C-T is Benign according to our data. Variant chr4-182753544-C-T is described in ClinVar as Benign. ClinVar VariationId is 257353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.505 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4 link	c.3957C>T	p.Gly1319Gly	synonymous_variant	Exon 21 of 28	ENST00000511685.6	NP_001073946.1	Q9P273A0A140VJW8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6 link	c.3957C>T	p.Gly1319Gly	synonymous_variant	Exon 21 of 28	5	NM_001080477.4	ENSP00000424226.1		Q9P273
TENM3	ENST00000502950.1 link	n.2365C>T		non_coding_transcript_exon_variant	Exon 14 of 15	2

Frequencies

GnomAD3 genomes

AF:

0.180

AC:

27406

AN:

152022

Hom.:

2765

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0881

Gnomad AMI

AF:

0.374

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.243

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.225

GnomAD2 exomes

AF:

0.197

AC:

49053

AN:

248714

AF XY:

0.203

show subpopulations

Gnomad AFR exome

AF:

0.0862

Gnomad AMR exome

AF:

0.133

Gnomad ASJ exome

AF:

0.242

Gnomad EAS exome

AF:

0.178

Gnomad FIN exome

AF:

0.224

Gnomad NFE exome

AF:

0.224

Gnomad OTH exome

AF:

0.218

GnomAD4 exome

AF:

0.212

AC:

309513

AN:

1460306

Hom.:

33687

Cov.:

AF XY:

0.212

AC XY:

154277

AN XY:

726420

show subpopulations

African (AFR)

AF:

0.0875

AC:

2926

AN:

33456

American (AMR)

AF:

0.143

AC:

6372

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.253

AC:

6595

AN:

26104

East Asian (EAS)

AF:

0.179

AC:

7118

AN:

39656

South Asian (SAS)

AF:

0.203

AC:

17467

AN:

86068

European-Finnish (FIN)

AF:

0.222

AC:

11862

AN:

53370

Middle Eastern (MID)

AF:

0.251

AC:

1447

AN:

5766

European-Non Finnish (NFE)

AF:

0.219

AC:

242865

AN:

1110898

Other (OTH)

AF:

0.213

AC:

12861

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

12025

24049

36074

48098

60123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8286

16572

24858

33144

41430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.180

AC:

27418

AN:

152140

Hom.:

2765

Cov.:

AF XY:

0.182

AC XY:

13521

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0880

AC:

3655

AN:

41530

American (AMR)

AF:

0.194

AC:

2969

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

842

AN:

3468

East Asian (EAS)

AF:

0.173

AC:

894

AN:

5160

South Asian (SAS)

AF:

0.211

AC:

1014

AN:

4816

European-Finnish (FIN)

AF:

0.220

AC:

2330

AN:

10586

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.218

AC:

14822

AN:

67978

Other (OTH)

AF:

0.225

AC:

475

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1169

2337

3506

4674

5843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

296

592

888

1184

1480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.200

Hom.:

7380

Bravo

AF:

0.174

Asia WGS

AF:

0.182

AC:

632

AN:

3478

EpiCase

AF:

0.225

EpiControl

AF:

0.238

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 19, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Microphthalmia, isolated, with coloboma 9

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

5.1

(source)

DANN

Benign

0.53

PhyloP100

-0.51

Mutation Taster

=88/12

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over